Deflazacort in Dysferlinopathies - Full Text View

Purpose

The present study is designed to assess the natural history in a one year pre-phase of the trial and evaluate therapeutic efficacy and side effects of deflazacort in LGMD2B/MM patients in a placebo-controlled trial. Furthermore, long-term development of the disease under naturalistic conditions will be documented in a 2-year follow-up after the end of the double-blind treatment phase.

Condition	Intervention	Phase
LGMD2B Miyoshi Myopathy Dysferlinopathy	Drug: deflazacort Drug: placebo	Phase 2 Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Crossover Assignment Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Deflazacort in Dysferlinopathies (LGMD2B/MM) - a Double Blind, Placebo-controlled Clinical Study

Resource links provided by NLM:

Genetics Home Reference related topics: Miyoshi myopathy

Drug Information available for: Deflazacort

Genetic and Rare Diseases Information Center resources: Muscular Dystrophy Limb-girdle Muscular Dystrophy Type 2A Dysferlinopathy Miyoshi Myopathy Limb-girdle Muscular Dystrophy, Type 2B

U.S. FDA Resources

Further study details as provided by Maggie Walter, Ludwig-Maximilians - University of Munich:

Primary Outcome Measures:

Muscle strength according to Medical Research Council Scales (MRC) and quantitative strength measurement evaluated by hand-held dynamometry (Citec, Groningen, The Netherlands)in the same muscle groups. [ Time Frame: each 6 months ]

Secondary Outcome Measures:

Quantitative strength measurement (QSM, M3diagnos, Fa. Schnell, Germany), Neuromuscular Symptoms Score (NSS), timed function tests, Clinical Global Impressions (CGI) of change and quality of life assessment(SF-36 scale). [ Time Frame: each 6 months ]


Enrollment:	25
Study Start Date:	September 2003
Study Completion Date:	September 2008
Primary Completion Date:	April 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: A After 6 months of treatment, and a 3-months wash-out, there is cross-over to Arm B	Drug: deflazacort In the first 12 months, patients will receive no treatment to assess the natural history of the disease. Afterwards, patients will be treated with deflazacort 1mg/kg/day or placebo for the first month on treatment, from the second month on deflazacort or placebo will be administered on an alternate day regimen). Patients will be randomized to six months verum or placebo each, after a 3-months wash-out patients cross over to the alternate treatment for six months. In a 2-years follow-up phase after the double-blind treatment phase, long-term development of the disorder will be documented. Other Names: Calcort Corticosteroid
Placebo Comparator: B After 6 months of treatment, and a 3-months wash-out, there is cross-over to Arm A	Drug: placebo

Arms

Assigned Interventions

Active Comparator: A

After 6 months of treatment, and a 3-months wash-out, there is cross-over to Arm B

Drug: deflazacort

In the first 12 months, patients will receive no treatment to assess the natural history of the disease. Afterwards, patients will be treated with deflazacort 1mg/kg/day or placebo for the first month on treatment, from the second month on deflazacort or placebo will be administered on an alternate day regimen). Patients will be randomized to six months verum or placebo each, after a 3-months wash-out patients cross over to the alternate treatment for six months. In a 2-years follow-up phase after the double-blind treatment phase, long-term development of the disorder will be documented.

Other Names:

Calcort
Corticosteroid

Placebo Comparator: B

After 6 months of treatment, and a 3-months wash-out, there is cross-over to Arm A

Drug: placebo

Detailed Description:

Limb girdle muscular dystrophies (LGMDs) are a genetically heterogeneous group of disorders encompassing various genetically defined subtypes (LGMD 2A-2H). Therapeutic trials should address each disease entity separately to assess effectiveness of medical treatments. A placebo-controlled trial in patients with dysferlinopathy may reveal insights in the natural course of the disease and show therapeutic options in a homogeneous group of patients. So far, steroids are the only drugs showing efficacy in muscular dystrophies, mainly in Duchenne muscular dystrophy (DMD). Both dystrophin and dysferlin are attached to the sarcolemma and deficiency of both proteins cause sarcolemmal defects; therefore, any membrane-stabilizing steroid effect may be beneficial in both DMD and LGMD2B/ Myoshi myopathy (MM). Furthermore, there is marked inflammation in muscle biopsies of many LGMD2B patients. Therefore, the anti-inflammatory effect of steroids may improve muscle function in LGMD2B/MM. In our trial, effects of deflazacort in patients with dysferlinopathy (LGMD2B/MM) on strength and daily-life activities are addressed. The present study is designed to assess the natural history and evaluate therapeutic efficacy and side effects of deflazacort / placebo in LGMD2B/MM patients.

Although no major therapeutic breakthrough has been achieved and curative treatment modalities are not yet applicable, life expectancy and quality of life of dysferlinopathy patients could be remarkably improved by establishing a drug therapy, capable of delaying the dystrophic process and improving muscle strength and function. Therefore, the results of this study are warranted and may influence further guidelines for steroid treatment in dysferlinopathies. Furthermore, the assessment of the natural history of the disease will provide new insights in the clinical understanding of dysferlinopathies.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Clinically, histologically, immunohistochemically and genetically defined muscular dystrophy with dysferlin-deficiency (LGMD2B/MM).
Patients should fulfill clinical, morphological, immunohistochemical and immunoblot criteria of LGMD 2B and definite mutation in dysferlin gene.
There is no limitation on age for study inclusion.

Exclusion Criteria:

Patients confined to bed or wheelchair.
Patients with other neurologic or internistic diseases and patients with former or current steroid treatment will not be included.
Exclusion criteria during the trial are withdrawal of informed consent or lack of compliance.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00527228

Locations


Germany
Friedrich-Baur-Institute, Dept. of Neurology, Ludwig-Maximilians-University of Munich
Munich, Germany, 80801

Sponsors and Collaborators

Ludwig-Maximilians - University of Munich

Investigators


Principal Investigator:	Maggie C. Walter, MD	Friedrich-Baur-Institute, Dept. of Neurology, Ludwig-Maximilians-University of Munich, Germany

More Information

Additional Information:

Homepage of the German Muscular Dystrophy Network (MD-NET) This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Walter MC, Reilich P, Thiele S, Schessl J, Schreiber H, Reiners K, Kress W, Müller-Reible C, Vorgerd M, Urban P, Schrank B, Deschauer M, Schlotter-Weigel B, Kohnen R, Lochmüller H. Treatment of dysferlinopathy with deflazacort: a double-blind, placebo-controlled clinical trial. Orphanet J Rare Dis. 2013 Feb 14;8:26. doi: 10.1186/1750-1172-8-26.


Responsible Party:	Maggie Walter, Prof. Dr. Maggie C. Walter, MD, MA, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier:	NCT00527228 History of Changes
Other Study ID Numbers:	274/02
Study First Received:	September 6, 2007
Last Updated:	August 31, 2015

Keywords provided by Maggie Walter, Ludwig-Maximilians - University of Munich:


Muscular dystrophy therapy steroids deflazacort	dysferlinopathy LGMD MM

Additional relevant MeSH terms:


Muscular Dystrophies, Limb-Girdle Muscular Dystrophies Muscular Disorders, Atrophic Muscular Diseases Musculoskeletal Diseases Neuromuscular Diseases Nervous System Diseases	Genetic Diseases, Inborn Deflazacort Anti-Inflammatory Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 23, 2017